Peroxisome proliferator-activated receptor gamma interacts with CIITA x RFX5 complex to repress type I collagen gene

Yong Xu1, Stephen R Farmer, Barbara D Smith

  • 1Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.

Insights

Peroxisome proliferator-activated receptor gamma (PPARgamma) represses collagen synthesis. PPARgamma interacts with CIITA to regulate collagen and MHC II expression, offering therapeutic targets for matrix remodeling and immune response diseases.

Area of Science:

  • Molecular Biology
  • Immunology
  • Cell Biology

Background:

  • Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor superfamily member.
  • PPARgamma has been reported to repress type I collagen synthesis.
  • Interferon-gamma (IFN-gamma) represses collagen gene expression and induces major histocompatibility complex II (MHC II) expression.

Purpose of the Study:

  • To investigate the role of PPARgamma in collagen synthesis regulation.
  • To determine the mechanism by which IFN-gamma represses collagen expression.
  • To explore PPARgamma as a potential therapeutic target.

Main Methods:

  • Exogenous expression and silencing of PPARgamma in human lung fibroblast cells.
  • Co-immunoprecipitation and DNA affinity precipitation assays.
  • Treatment with PPARgamma agonist (troglitazone) and antagonist (T0070907).

Main Results:

  • Exogenous PPARgamma down-regulates collagen expression in a dose-dependent manner.
  • Silencing PPARgamma reverses IFN-gamma-induced collagen repression.
  • PPARgamma is part of the RFX5.CIITA complex and its occupancy increases with IFN-gamma treatment.
  • PPARgamma agonist enhances IFN-gamma effects, while antagonist blocks them.

Conclusions:

  • PPARgamma mediates IFN-gamma-induced collagen transcription down-regulation and MHC II up-regulation.
  • PPARgamma interacts with CIITA to regulate collagen and MHC II expression.
  • PPARgamma is a critical target for diseases involving extracellular matrix remodeling and immune response.

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